Chemotherapy has been used, with varying success, in the treatment of metastatic cancers. However, a major problem with many chemotherapeutic agents is their damage to normal cells and organs, poor selectivity for neoplastic cells and multidrug resistance upon prolonged treatment (Rooseboom et al. (2004). Pharmaceutical Reviews 56, pp. 53-102).
One strategy to overcome the limitations of chemotherapeutic agents is to conjugate one or more agents to an antibody, which is specific for a cell type or tissue. Antibody-drug conjugates (ADCs) have been used as a more rational approach to targeting cytotoxic agents to cells. Both polyclonal and monoclonal antibodies can be used in ADCs. In an ADC, one or more drug molecules are covalently bonded to an antibody (or fragment thereof).
ADCs have been used to enhance the antitumor activity of antibodies as well as to reduce the systemic toxicity of drugs. Antibody targeted therapy is advantageous because the epitope(s) recognized by the antibody is typically over-expressed on a tumor cell, or only expressed on the tumor cell. Therefore, conjugating a drug (e.g., a chemotherapeutic agent) to an antibody allows the delivery of the drug, to the tissue or specific cell type of interest. The antibody portion of the conjugate specifically binds the target of interest, while the drug portion of the conjugate exerts its effects in the cell tissue to which the antibody binds. Once the antibody is bound to the target cell-surface antigen, the conjugate is processed to release an active form of the drug, which can reach its intracellular target.
Although ADCs have been used in cancer therapy, rapid and reliable methods are lacking for determining the amount of drug molecule present in an ADC complex. The present invention addresses this and other needs.